The present proposal is for continued funding for a Specialized Center of Research in Hematopoietic Stem Cell Biology at the Children's Hospital Long Angeles (CHLA) and the University of California Los Angeles (UCLA). The programmatic focus of the proposal is to increase our understanding of hematopoietic (HSC) differentiation with the ultimate goal of improving the therapy of patients with hematological, immunological, and genetic diseases. The proposal is multi-disciplinary clinical HSC transplantation. The proposal contains four Projects and three Cores including an Administrative Core that contains a Pilot Project. The Specific Aims of the Projects include 1) the regulation of human HSC cell cycle induction, 2) the regulation of HSC differentiation, 3) the role of cytokine receptor interactions in lymphohematopoietic differentiation, 4) an evaluation of HSC transduction by lentivirus vectors, and 5) a clinical gene therapy trial for adenosine deaminase (ADA) vectors. Overall the proposal is an integration of basic/pre-clinical laboratory research and clinical utilization of HSC.